Purificatton of a neutral endopeptidase cleaving internal bonds of somatostatin and lutneizing hormone releasing hormone (LH-RH) will be undertaken with emphasis placed on a new procedure involving isoelectric focusing on Sephadex columns. To further elucidate the role of degradation in regulation of hypothalamic releasing factors enzyme will be tested using newer cyclic analogs of somatostatin: cyclo (amino-heptanoyl-D-Trp8) and des (Ala1Gly2)-desamino (Cys3)-descorboxy (Cys14)dicarbo3,14. Attention will be directed at isolation and charaterization of enzymes involved in conversion of prohormones such as angiotensin-I, and beta-lipotropin to yield active fragments such as angiotensin-II, alpha-MSH and related lipotropic peptides. Brain is known to contain an autonomous angiotensin-renin system but enzymes involved have never been purified. It has been postulated that brain contains tryptic and neutral-like proteases capable of converting beta-lipotropin with biologically active fragments. Enzymes inactivating thryrotropic releasing hormone (TRH) include pyroglutamyl peptidase, peptidases and deamidases. An attempt will be made to purify the amidase from brain regions since this enzyme appears to be the primary one involved in the inactivation process. BIBLIOGRAPHIC REFERENCES: Grynvaum, A. and Marks, N. "Characterization of a rat brain catheptic carbosypeptidase (cathepsin A) inactivating angiotensin-II" J. Neurochem. 26: 313-318, 1976. Marks, N., Gynbaum, A. and Benuck, M. "On the sequential cleavage of myelin basic protein by cathepsins A and D" J. Neurochem. 27: 763-768, 1976.